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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 225-230, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38387926

RESUMO

OBJECTIVE: To study the serological characteristics of ABO*A2.08 subtype and explore its genetic molecular mechanism. METHODS: ABO blood group identification was performed on proband and her family members by routine serological methods. ABO genotyping and sequence analysis were performed by polymerase chain reaction-sequence specific primer (PCR-SSP), and direct sequencing of PCR products from exons 6 and 7 of ABO gene were directly sequenced and analyzed. The effect of gene mutation in A2.08 subtype on structural stability of GTA protein was investigated by homologous protein conserved analysis, 3D molecular modeling and protein stability prediction. RESULTS: The proband's serological test results showed subtype Ax, and ABO genotyping confirmed that the proband's genotype was ABO*A207/08. Gene sequencing of the proband's father confirmed the characteristic variation of c.539G>C in the 7th exon of ABO gene, leading to the replacement of polypeptide chain p.Arg180Pro (R180P). 3D protein molecular modeling and analysis suggested that the number of hydrogen bonds of local amino acids in the protein structure was changed after the mutation, and protein stability prediction showed that the mutation had a great influence on the protein structure stability. CONCLUSION: The mutation of the 7th exon c.539G>C of ABO gene leads to the substitution of polypeptide chain amino acid, which affects the structural stability of GTA protein and leads to the change of enzyme activity, resulting in the A2.08 phenotype. The mutated gene can be stably inherited.


Assuntos
Peptídeos , Humanos , Recém-Nascido , Feminino , Alelos , Sequência de Bases , Genótipo , Fenótipo
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(1): 215-220, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36765502

RESUMO

OBJECTIVE: To analyze the characteristics of antibody-specific distribution, laboratory detection results of hemolytic disease of the fetus and neonatal(HDFN) caused by irregular blood group antibodies other than ABO, and its correlation with the clinical situation. METHODS: The non-ABO-HDFN cases in our hospital from October 2012 to December 2021 were selected as the research objects, and the cases diagnosed with ABO-HDFN in the same period were randomly selected as the control group, and the data of antibody specific distribution, total bilirubin, direct antibodies, maternal history, age of the children, the presence or absence of combined ABO-HDFN, and whether to exchange/transfuse blood were retrospectively analyzed. The characteristics of non-ABO-HDFN in Jiangxi province were analyzed. RESULTS: The detection rate of non-ABO-HDFN in Jiangxi province increased. Among 187 non ABO-HDFN cases, the highest percentage of Rh-HDFN was detected (94.6%). Compared with the control group of ABO-HDFN, the non-ABO-HDFN had higher mean integral value of direct antibody, higher peak total bilirubin, and longer duration. Anti-M-HDFN may have severe disease but the direct antibody weak positive/negative, it was easy missed in clinical and delayed the treatment. There is no correlation between the specificity of irregular antibodies, the sex of the child, the mother's previous childbirth history, the presence or absence of combined ABO-HDFN and the need for blood exchange/transfusion(P>0.05). CONCLUSION: The irregular antibodies of causing non ABO-HDFN in Jiangxi area are mainly Rh blood group system, followed by MNS blood group system. Understanding the characteristics of HDFN disease, serological features and the correlation with clinical indexes will help to detect and treat non ABO-HDFN in time and reduce the risk of complications.


Assuntos
Antígenos de Grupos Sanguíneos , Eritroblastose Fetal , Doenças Hematológicas , Criança , Feminino , Humanos , Recém-Nascido , Sistema ABO de Grupos Sanguíneos , Feto , Doenças Hematológicas/complicações , Hemólise , Isoanticorpos , Estudos Retrospectivos
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(6): 1839-1844, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36476913

RESUMO

OBJECTIVE: To explore the molecular biology of D variant blood group with RHD*95A genotype and the genetic mechanism of its generation. METHODS: A total of 6 samples from 3 generations of a family were analyzed. RHD blood group was identified by saline test tube and microcolumn gel card method. 10 exons of RHD gene were amplified by Polymerase Chain Reaction-Sequence Specific Primer (PCR-SSP) and analyzed by direct sequencing. Homology modeling was used to compare the structural differences between mutant RHD protein and wild-type RHD protein. RESULTS: The proband was identified as D variant by serological identification, RHD gene sequencing directly detected a c. 95 c > A mutation in exon 1 that leads to encoding the 32-bit amino acids by threonine Thr (T) into aspartic acid Asn (N), the rest of the exon sequences were normal compared with the normal RHD*01 gene. In the family, the proband's father, grandmather and uncle were all carried the same RHD*95A allele. Protein modeling results suggested that the hydrogen chain connected to the 32nd amino acid residue was changed after p.T32N mutation, which affected the structural stability of RHD protein. CONCLUSION: The first genetic lineage of the RHD*95A gene was identified in a Chinese population. The c.95C>A mutation in RHD gene was found in the family, which resulted in reduced expression of RHD antigen and showed D variant, the mutation could be stably inheritable. Gene identification and protein structure analysis of D variant population is helpful to explore the molecular mechanism of its formation and ensure the safety of blood transfusion.


Assuntos
Antígenos de Grupos Sanguíneos , Humanos
4.
Mitochondrial DNA B Resour ; 7(12): 2027-2030, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518736

RESUMO

The morphological characteristic of Dendrobium moschatum (Buch.-Ham.) Sw. 1805 is very distinctive among Dendrobium Sw. 1799, and it has high medicinal and ornamental values. Here, we reported the first complete chloroplast genome of D. moschatum. The complete genome of D. moschatum was 159,701 bp in length with 130 genes, including 38 tRNA, 8 rRNA, and 84 protein-coding genes. Phylogenetic analysis showed that D. moschatum was strongly allied with D. denneanum Kerr. 1933.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(5): 1557-1561, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36208265

RESUMO

OBJECTIVE: To investigate the effect of ABO gene α-1,3-D galactosyl transferase mutation on B antigen expression and its molecular mechanism. METHODS: The proband and their family members were identified by routine serological methods, and ABO genotyping and sequence analysis were performed by polymerase chain reaction-sequence specificity (PCR-SSP) and direct sequencing of PCR products from exon 1-7 of ABO gene. The 3D structural simulation of mutant proteins was performed by bioinformatics software. The effect of gene mutation on protein structural stability was analyzed. RESULTS: The proband and his family members were subtype B. ABO genotyping indicated that the proband's genotype was Bw12/O. Gene sequencing results confirmed the presence of ABO*BW.12 characteristic variation c.278C>T in the 6th exon of allele B, leading to the replacement of polypeptide chain p.Pro93Leu. The 3D structure simulation analysis of the protein showed that the hydrogen bonds and water molecules connected to the protein changed after amino acid substitution. The family investigation found that the grandfather, father, uncle and brother of the proband all carried the same ABO*BW.12 allele. CONCLUSION: The mutation of the 6th exon c.278C>T of ABO gene led to the substitution of polypeptide chain amino acids, which affected the stability of α-1,3-D galactosyl transferase protein, resulting in the change of enzyme activity, and the Bw.12 phenotype, which can be stably inherited.


Assuntos
Sistema ABO de Grupos Sanguíneos , Aminoácidos , Sistema ABO de Grupos Sanguíneos/genética , Alelos , Aminoácidos/genética , Animais , Sequência de Bases , Éxons , Genótipo , Masculino , Proteínas Mutantes/genética , Mutação , Fenótipo , Água
6.
Plant Signal Behav ; 17(1): 2005882, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-34913407

RESUMO

Seed germination and seedling development in nearly all orchid species rely on a symbiotic relationship with mycorrhizal fungi; however, this is not the case with all mycorrhizal fungi. This study aims to provide an understanding about the important role of mycorrhiza in seed germination and growth of Paphiopedilum barbigerum. Therefore, we isolated and identified endophytic fungi from the roots of wild P. barbigerum. The beneficial mycorrhizal fungi Epulorhiza sp. FQXY019 and Tulasnella calospora FQXY017 were screened by seed symbiotic germination tests and found to promote seed germination. However, only the seeds inoculated with FQXY019 progressed from the seed germination to rooting stage. This shows that mycorrhizal fungi and P. barbigerum have a specific relation at different growth phases. In addition, we selected FQXY019 and inoculated it into MS medium, B5 medium, OMA medium, and PDA medium. The results showed that FQXY019 co-cultured on PDA significantly promoted the increase in seedling fresh weight, leaf length, and root length (p < .01). Furthermore, it significantly promoted the root number and leaf number of seedlings compared with those co-cultured on MS, B5, and OMA media and control (p < .05). Thus, this study demonstrated the promoting effect of Epulorhiza sp. FQXY019 on seed germination and seedling development, making it an alternative method for the artificial propagation of P. barbigerum.


Assuntos
Micorrizas , Orchidaceae , Germinação , Orchidaceae/microbiologia , Plântula , Sementes , Simbiose
7.
Carbohydr Polym ; 268: 118257, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34127228

RESUMO

Multifunctional theranostic nanoplatforms integrated of imaging function, multi-modality therapy, stimuli-responsiveness, and targeted delivery are of highly desirable attributes in achieving precise medicine. However, preparation of multifunctional nanoplatforms often involves laborious, multiple steps and inevitably utilizes low-biocompatible or non-functional components. Herein we report a facile, one-step self-assembly strategy to fabricate hyaluronic acid (HA)-based multifunctional tumor theranostic nanoplatform by employing magnetic resonance imaging (MRI) agent Mn2+ as a reversible crosslink agent for histidine-grafted HA, along with simultaneously loading chemotherapeutic agent doxorubicin hydrochloride (DOX) and photodynamic therapy agent chlorin e6, to realize MRI-guided targeted chemo-photodynamic cancer therapy. The targeted delivery and stimuli-responsive payload release were demonstrated in vitro and in vivo. Furthermore, the combined chemo-photodynamic therapy of the nanoassembly dramatically improved the cancer therapeutic outcome, in comparison with that of free DOX and nanoplatform solely loaded DOX in a melanoma bearing mice. Our one step assemble strategy is of great potential in clinic transformation.


Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Nanogéis/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Linhagem Celular Tumoral , Clorofilídeos , Doxorrubicina/uso terapêutico , Portadores de Fármacos/toxicidade , Histidina/química , Histidina/toxicidade , Ácido Hialurônico/análogos & derivados , Ácido Hialurônico/toxicidade , Luz , Manganês/química , Manganês/toxicidade , Camundongos Endogâmicos C57BL , Nanogéis/toxicidade , Fotoquimioterapia , Fármacos Fotossensibilizantes/efeitos da radiação , Porfirinas/efeitos da radiação , Porfirinas/uso terapêutico , Medicina de Precisão/métodos , Oxigênio Singlete/metabolismo
8.
Chem Sci ; 12(22): 7727-7734, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-34168825

RESUMO

Aggregation-induced emission (AIE) based fluorophores (AIEgens) have attracted increasing attention for biomedical applications due to their unique optical properties. Here we report an AIE photosensitizer functionalized CB[7], namely AIECB[7], which could spontaneously self-assemble into nanoaggregates in aqueous solutions. Interestingly, the carbonyl-lace of CB[7] may potentially act as a proton acceptor in an acidic environment to fine-tune the fluorescence and singlet oxygen generation of AIECB[7] nanoaggregates by regulating the inner stacking of AIEgens. Additionally, benefiting from the guest-binding properties of CB[7], oxaliplatin was included into AIECB[7] nanoaggregates for combined photodynamic therapy and supramolecular chemotherapy. To show the modular versatility of this supramolecular system, a hypoxia-activatable prodrug banoxantrone (AQ4N) was loaded into AIECB[7] nanoaggregates, which exhibited synergistic antitumor effects on a multicellular tumor spheroid model (MCTS). This work not only provides AIECB[7] for versatile theranostic applications, but also offers important new insights into the design and development of macrocycle-conjugated AIE materials for diverse biomedical applications.

9.
Biomater Sci ; 9(10): 3804-3813, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33881050

RESUMO

Nano-graphene oxide (NGO) has attracted increasing attention as an advanced drug delivery system. However, the current surface functionalization and drug-loading of NGO either rely on π-π stacking that is limited to aromatic molecules, or covalent conjugation that requires tedious synthesis. Herein, we developed the first cucurbit[7]uril (CB[7])-conjugated NGO (NGO-CB[7]) that allows non-covalent, modular surface functionalization and drug loading via not only traditional π-π stacking interactions between the NGO surface and functional molecules, but also strong host-guest interactions between CB[7] and guest payloads or adamantane (ADA)-tagged functional molecules, for more versatile biomedical applications. To this end, chlorin e6 (Ce6, a photosensitizer), banoxantrone dihydrochloride (AQ4N, a hypoxia-responsive prodrug) and oxaliplatin (OX, a guest of CB[7]) were co-loaded onto NGO-CB[7] via π-π stacking and host-guest interactions, respectively. Subsequently, ADA-tagged hyaluronic acid (ADA-HA) wrapped NGO-CB[7] non-covalently via CB[7]-ADA host-guest interactions to improve the physiological stability and overall biocompatibility of this supramolecular nanosystem, and to enable targeted delivery into cancer cells with CD44 receptors overexpressed. Remarkably, this supramolecular nanomedicine exhibited significant antitumor efficacy via combined photothermal/photodynamic therapy (PTT/PDT) from NGO/Ce6, as well as dual chemotherapy from OX and AQ4N (activated by PDT-enhanced hypoxia), in vitro and in vivo. This study not only offers a new supramolecular inorganic/organic hybrid nanosystem for multi-modality cancer therapy, but may also provide important new insights into noncovalent functionalization of other carbon nanomaterials and inorganic nanomaterials leading to multifunctional drug delivery systems.


Assuntos
Nanomedicina , Neoplasias , Hidrocarbonetos Aromáticos com Pontes , Imidazóis , Neoplasias/tratamento farmacológico , Óxidos
10.
ACS Appl Mater Interfaces ; 11(32): 28665-28670, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31381300

RESUMO

Polysaccharide-based nanogels have drawn considerable interest in pharmaceutics because of their superior biocompatibility and potential responsiveness to external stimuli, enabling specific drug release. During the fabrication of nanogels, however, covalent cross-linking often involves less friendly cross-linkers and traditionally employed noncovalent cross-linking often relies on weak interactions that may lead to premature payload release. Herein, we report host-guest chemistry-driven supramolecular chitosan nanogels (CNGs) that are responsive to either endogenous or exogenous stimuli, thus allowing selective drug release in specific cancer cells or disease sites. In an aqueous solution, two phenylalanine (Phe) units of Phe-grafted chitosan (CS-Phe) were encapsulated into one cavity of cucurbit[8]uril (CB[8]), driving cross-linking of CS-Phe and formation of CNGs. Doxorubicin hydrochloride (DOX), a chemotherapeutic agent, was entrapped in the matrix of CNGs during the formation of nanogels to yield DOX-CNGs with an excellent drug loading efficiency. The morphology and size of CNGs were fully assessed by transmission electron microscopy and dynamic light scattering. The encapsulated DOX was selectively liberated in the presence of competitive guests of CB[8], such as endogenous spermine (SPM) that is overexpressed by certain types of cancer cells or exogenous amantadine (ADA) that may be added into cells or tissues that require targeted treatment, either of which may replace Phe from the cavity of CB[8] resulting in the breakdown of the nanogels and payload release. The CNGs were efficiently internalized by cells, and the DOX-CNGs exhibited specific, potent activity against cancerous cells such as A549 cell line that is well known for SPM overexpression. This study reports that the first stimuli (competitive guest)-responsive host-guest interactions initiated supramolecular CNGs with excellent biocompatibility and selective therapeutic efficacy against cancer cells. It may provide new insights into the design and fabrication of novel stimuli-responsive payload delivery systems.


Assuntos
Quitosana , Doxorrubicina , Sistemas de Liberação de Medicamentos , Nanoestruturas , Neoplasias , Células A549 , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Géis , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia
11.
Biomed Environ Sci ; 32(3): 199-209, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30987694

RESUMO

OBJECTIVE: To evaluate the synergy of the Burkholderia signaling molecule cis-2-dodecenoic acid (BDSF) and fluconazole (FLU) or itraconazole (ITRA) against two azole-resistant C. albicans clinical isolates in vitro and in vivo. METHODS: Minimum inhibitory concentrations (MICs) of antibiotics against two azole-resistant C. albicans were measured by the checkerboard technique, E-test, and time-kill assay. In vivo antifungal synergy testing was performed on mice. Analysis of the relative gene expression levels of the strains was conducted by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). RESULTS: BDSF showed highly synergistic effects in combination with FLU or ITRA with a fractional inhibitory concentration index of ⪕ 0.08. BDSF was not cytotoxic to normal human foreskin fibroblast cells at concentrations of up to 300 µg/mL. The qRT-PCR results showed that the combination of BDSF and FLU/ITRA significantly inhibits the expression of the efflux pump genes CDR1 and MDR1 via suppression of the transcription factors TAC1 and MRR1, respectively, when compared with FLU or ITRA alone. No dramatic difference in the mRNA expression levels of ERG1, ERG11, and UPC2 was found, which indicates that the drug combinations do not significantly interfere with UPC2-mediated ergosterol levels. In vivo experiments revealed that combination therapy can be an effective therapeutic approach to treat candidiasis. CONCLUSION: The synergistic effects of BDSF and azoles may be useful as an alternative approach to control azole-resistant Candida infections.


Assuntos
Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Farmacorresistência Fúngica , Ácidos Graxos Monoinsaturados/efeitos adversos , Fluconazol/farmacologia , Triazóis/metabolismo , Burkholderia cenocepacia/química , Candida albicans/fisiologia , Candidíase/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana
12.
ACS Appl Bio Mater ; 2(6): 2421-2434, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35030699

RESUMO

Self-assembled hyaluronic acid (HA) nanoparticles have been extensively investigated as anticancer therapeutic agents due to the biocompatibility, biodegradability, and active targeting characteristics of HA. However, many HA nanoparticles are restricted to the applications in drug delivery for chemotherapy or lack effective imaging agents. Hence, we developed the camptothecin (CPT)-loaded HA-SS-BFVPBT nanoparticles (HSBNPs) as a multifunctional platform for two-photon imaging and synergistic chemo-photodynamic therapy at the same time. A novel conjugated oligomer photosensitizer, BFVPBT, which was conjugated onto HA through the redox-responsive disulfide linkage (SS), could not only provide a hydrophobic domain for the formation of nanoparticles and drug entrapment but also act as a two-photon photosensitizer that can be directly excited and simultaneously used in two-photon imaging and photodynamic therapy (PDT). HeLa cells overexpressing the HA receptor (CD44) were used for in vitro studies, which proved the specific cellular uptake of CPT-loaded HSBNPs and excellent two-photon PDT/chemotherapy synergistic effect. The nanoparticles have also been shown to realize tumor-targeting in vivo imaging in HeLa-tumor-bearing mice. Moreover, the fluorescence of CPT-loaded HSBNPs could be activated due to the degradation by the reductive glutathione (GSH) and overexpressed hyaluronidases (Hyal-1) in cancer cells, and the intracellular drug release rate was quickened, thus improving the probability of precise cancer diagnosis and therapy. Accordingly, this HSBNPs system is also anticipated to be a precise nanocarrier for other imaging and therapeutic agents besides CPT, offering a promising new avenue for imaging-guided efficient cancer therapy.

13.
Biomed Environ Sci ; 31(11): 816-828, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30558702

RESUMO

OBJECTIVE: To evaluate the efficacy of cis-2-dodecenoic acid (BDSF) in the treatment and prevention of vaginal candidiasis in vivo. METHODS: The activities of different concentrations of BDSF against the virulence factors of Candida albicans (C. albicans) were determined in vitro. An experimental mouse model of Candida vaginitis was treated with 250 µmol/L BDSF. Treatment efficiency was evaluated in accordance with vaginal fungal burden and inflammation symptoms. RESULTS: In vitro experiments indicated that BDSF attenuated the adhesion and damage of C. albicans to epithelial cells by decreasing phospholipase secretion and blocking filament formation. Treatment with 30 µmol/L BDSF reduced the adhesion and damage of C. albicans to epithelial cells by 36.9% and 42.3%, respectively. Treatment with 200 µmol/L BDSF completely inhibited phospholipase activity. In vivo mouse experiments demonstrated that BDSF could effectively eliminate vaginal infection and relieve inflammatory symptoms. Four days of treatment with 250 µmol/L BDSF reduced vaginal fungal loads by 6-fold and depressed inflammation. Moreover, BDSF treatment decreased the expression levels of the inflammatory chemokine-associated genes MCP-1 and IGFBP3 by 2.5- and 2-fold, respectively. CONCLUSION: BDSF is a novel alternative drug that can efficiently control vaginal candidiasis by inhibiting the virulence factors of C. albicans.


Assuntos
Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Ácidos Graxos Monoinsaturados/administração & dosagem , Animais , Candida albicans/metabolismo , Candida albicans/patogenicidade , Candida albicans/fisiologia , Candidíase Vulvovaginal/genética , Candidíase Vulvovaginal/imunologia , Candidíase Vulvovaginal/microbiologia , Quimiocina CCL2/genética , Quimiocina CCL2/imunologia , Modelos Animais de Doenças , Feminino , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/imunologia , Camundongos , Virulência/efeitos dos fármacos , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
14.
ACS Appl Mater Interfaces ; 10(30): 25090-25098, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29993234

RESUMO

Surface functionalization of nanoparticles (NPs) is of pivotal importance in nanomedicine. However, current strategies often require covalent conjugation that involves laborious design and synthesis. Herein, cucurbit[7]uril (CB[7])-decorated poly(lactic acid) (PLA)/poly(lactic-co-glycolic acid) (PLGA) NPs are developed and exploited for the first time as a novel, biocompatible, and versatile drug delivery platform with a noncovalently tailorable surface. CB[7] on the surface of NPs, acting as a "Lego" base block, allowed facile, modular surface modification with a variety of functional moieties or tags that are linked with amantadine (a complementary "Lego" piece to the base block), including amantadine-conjugated folate, polyethylene glycol, and fluorescein isothiocyanate. In addition, surface CB[7] also provided an opportunity for encapsulation of a secondary drug, such as oxaliplatin, into the cavity of the base block CB[7], in addition to a primary drug (e.g., paclitaxel) loaded into PLA/PLGA NPs, for a possible synergistic chemotherapy. This proof of concept not only provides the first versatile PLA/PLGA nanomedicine platform with "Lego" surface for modular functionalization and improved drug delivery but also offers new insights into the design and development of novel nanomedicine with a modular surface.


Assuntos
Nanomedicina , Sistemas de Liberação de Medicamentos , Ácido Láctico , Nanopartículas , Polietilenoglicóis , Ácido Poliglicólico
15.
Sci Rep ; 8(1): 8819, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29891955

RESUMO

As one of the most water-soluble members in the macrocyclic cucurbit[n]uril (CB[n]) family, CB[7] has attracted increasing attention in pharmaceutical and biomedical fields. Despite extensive studies regarding the potential use of CB[7] for biomedical applications, its full safety and toxicity profile in a clinically relevant model is still lacking. Herein we report the full biocompatibility profile of CB[7], administered orally, peritoneally or intravenously in mice, respectively. Body-weight changes showed no significant differences among various groups of mice after they were administered with CB[7] at a single dose of 5 g/kg orally, 500 mg/kg peritoneally and 150 mg/kg intravenously, respectively. Hematology tests, as well as hepatic and renal function biochemical markers tests, of the blood collected from these mice sacrificed 21 days after CB[7] administration all exhibited normal ranges of values that were comparable with those of the control group. Moreover, histopathological analysis on the sections of major organs (including the heart, liver, spleen, lungs and kidneys) and gastrointestinal tissues revealed no detectable injuries and inflammatory cells infiltration. Taken together, these results suggest an excellent biocompatibility profile of CB[7] in mice, which provide important foundations for further investigations and even clinical applications of CB[7] in biomedical areas.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Teste de Materiais , Administração Intravenosa , Administração Oral , Estruturas Animais/patologia , Animais , Peso Corporal , Testes Hematológicos , Histocitoquímica , Injeções Intraperitoneais , Testes de Função Renal , Testes de Função Hepática , Camundongos
17.
Biomater Sci ; 6(5): 1031-1039, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29557458

RESUMO

Due to its outstanding capability to facilitate DNA condensation, transportation and endosomal escape, polyethylenimine (PEI) has been frequently studied for gene delivery. However, its molecular weight (M.W.) dependent transfection efficiency and cytotoxicity has severely limited its clinical application. To resolve this dilemma, a supramolecular strategy was developed for the first time, in which PEI with large M.W. (branched, 25 kDa) that has a satisfactory transfection efficiency, yet high non-specific cytotoxicity for gene delivery was wrapped with macrocyclic cucurbit[7]uril (CB[7]). The successful wrapping of the PEI by the macrocyclic CB[7] was proved by 1H NMR spectroscopy and supported by isothermal titration calorimetry (ITC). The plasmid DNA (pDNA) condensability of PEI was not affected by the supramolecular coating as evidenced from the agarose gel electrophoresis assay. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) results demonstrated that the particle size, zeta potential, and morphology of the self-assemblies of PEI/pDNA and PEI/CB[7]/pDNA were comparable. As a consequence of the supramolecular wrapping, the cytotoxicity of PEI was significantly constrained as demonstrated by MTT assay, apoptosis assay, and a hemolysis study. In particular, both the cellular uptake and the gene transfection efficiency results suggest that the supramolecular wrapping of PEI by CB[7] exhibits negligible effects on PEI, thus functioning as an effective non-viral gene delivery vector. This novel supramolecular-wrapping strategy provides new insights for facile alleviation of the non-specific toxicity of PEI and potentially other polycationic gene vectors without compromising their transfection efficiency.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Polietilenoimina/química , Transfecção/métodos , Apoptose/efeitos dos fármacos , Hidrocarbonetos Aromáticos com Pontes/toxicidade , Linhagem Celular Tumoral , Células HEK293 , Hemólise/efeitos dos fármacos , Humanos , Imidazóis/toxicidade , Plasmídeos/genética , Polietilenoimina/toxicidade
18.
ACS Appl Mater Interfaces ; 10(12): 9980-9987, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29498260

RESUMO

The photosensitizer Chlorin e6 (Ce6) has been frequently employed for photodynamic therapy (PDT) of cancer; however, its nonspecific toxicity has limited its clinical applications. In this study, we prepared chitosan nanoparticles (CNPs), with a mean diameter of approximately 130 nm, by a nonsolvent-aided counterion complexation method in an aqueous solution, into which Ce6 could be physically entrapped during the preparation process. These CNPs and Ce6-loaded CNPs (CNPs-Ce6) were fully characterized by UV-vis, photoluminescence, and Fourier transform infrared spectroscopic analysis, as well as dynamic light scattering and transmission electron microscopy measurements. More importantly, the biocompatibility of the otherwise toxic Ce6 was significantly improved upon its loading into the CNPs, as demonstrated by both confocal laser scanning microscopy analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Furthermore, the PDT efficiency of Ce6-loaded CNPs was dramatically enhanced, in comparison with that of the free Ce6, as shown by both MTT and flow cytometry assays. This discovery provides a novel strategy for improving the biocompatibility and therapeutic efficacy of PDT agents by using a natural, biocompatible polysaccharide carrier.


Assuntos
Nanopartículas , Quitosana , Clorofilídeos , Humanos , Neoplasias , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas
19.
Chem Asian J ; 13(1): 41-45, 2018 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-29181896

RESUMO

The teratogenicity of the pesticide nereistoxin (NTX) and its derivative thiocyclam (THI) towards aquatic life was dramatically constrained by a synthetic nanoreceptor, cucurbit[7]uril, through selective encapsulation of the pesticides (KCB[7]-NTX of 3.24(±0.31)×106 m-1 and KCB[7]-THI of 7.46(±0.10)×105 m-1 ), as evidenced by the rate of hatchability, morphology development, and tyrosinase activity of zebrafish larvae incubated with the pesticides (3-300 µm) in the absence and in the presence of 300 µm cucurbit[7]uril, demonstrating the significant potential of the nanoreceptor in managing ecological pollution of these pesticides.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/farmacologia , Compostos Heterocíclicos com 1 Anel/antagonistas & inibidores , Compostos Heterocíclicos com 1 Anel/toxicidade , Imidazóis/farmacologia , Toxinas Marinhas/antagonistas & inibidores , Toxinas Marinhas/toxicidade , Teratogênicos/toxicidade , Poluentes Químicos da Água/antagonistas & inibidores , Animais , Hidrocarbonetos Aromáticos com Pontes/química , Relação Dose-Resposta a Droga , Compostos Heterocíclicos com 1 Anel/química , Imidazóis/química , Larva/efeitos dos fármacos , Toxinas Marinhas/química , Estrutura Molecular , Relação Estrutura-Atividade , Teratogênicos/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
20.
ACS Appl Bio Mater ; 1(3): 544-548, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34996189

RESUMO

Hexadimethrine bromide (HB), a polycation to neutralize heparin and control internal bleeding, may also cause serious blood coagulation that may be life-threatening. Reversal of HB by heparin and vice versa might potentially lead to a vicious circle of alternative bleeding and blood coagulation. In this Letter, a biocompatible synthetic nanoreceptor, cucurbit[7]uril (CB[7]), was demonstrated to dramatically alleviate HB-induced blood coagulation in vitro as well as in vivo, through the formation of HB@CB[7] polypseudorotaxanes. This discovery, for the first time, suggests the significant clinical potential of a synthetic receptor in alleviating the side effects and toxicity of a polycationic drug.

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